suxamethonium chloride

スキサメトニウム

WordNet

1. any compound containing a chlorine atom
2. any salt of hydrochloric acid (containing the chloride ion)

PrepTutorEJDIC

1. 塩化物

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/07/01 01:59:21」(JST)

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Suxamethonium chloride

Systematic (IUPAC) name
2,2'-[(1,4-dioxobutane-1,4-diyl)bis(oxy)]bis (N,N,N-trimethylethanaminium)
Clinical data
Pronunciation	/ˌsʌksᵻnᵻlˈkoʊlin/
Trade names	Quelicin, Anectine
AHFS/Drugs.com	Monograph
Pregnancy category	AU: A US: C (Risk not ruled out)
Routes of administration	Intravenous, Intramuscular
Legal status
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	NA
Metabolism	By pseudocholinesterase, to succinylmonocholine and choline
Excretion	Renal (10%)
Identifiers
CAS Number	306-40-1 Y
ATC code	M03AB01 (WHO)
PubChem	CID 22475
IUPHAR/BPS	4004
DrugBank	DB00202 N
ChemSpider	21080 Y
UNII	J2R869A8YF Y
KEGG	D00766 Y
ChEBI	CHEBI:61219 Y
ChEMBL	CHEMBL983 Y
Chemical data
Formula	C14H30N2O4
Molar mass	290.399 g/mol
SMILES [Cl-].[Cl-].O=C(OCC[N+](C)(C)C)CCC(=O)OCC[N+](C)(C)C
InChI InChI=1S/C14H30N2O4.2ClH/c1-15(2,3)9-11-19-13(17)7-8-14(18)20-12-10-16(4,5)6;;/h7-12H2,1-6H3;2*1H/q+2;;/p-2 Y Key:YOEWQQVKRJEPAE-UHFFFAOYSA-L Y
NY (what is this?)  (verify)

Suxamethonium chloride, also known as suxamethonium or succinylcholine, is a medication used to induce muscle relaxation and short-term paralysis, usually to help with tracheal intubation. It is sometimes used in combination with pain medications and sedatives for euthanasia and immobilization of horses. It is colloquially referred to as "sux" in hospital settings.

Suxamethonium acts as a depolarizing neuromuscular blocker. It acts on nicotinic receptors resulting in persistent depolarization of the motor end plate. It is degraded by butyrylcholinesterase into succinic acid and choline. This hydrolysis by butyrylcholinesterase is much slower than that of acetylcholine by acetylcholinesterase.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.

Medical uses

A vial of suxamethonium chloride

Its medical uses are limited to short-term muscle relaxation in anesthesia and intensive care, usually for facilitation of endotracheal intubation. It is perennially popular in emergency medicine because it has the fastest onset and shortest duration of action of all muscle relaxants. The former is a major point of consideration in the context of trauma care, where endotracheal intubation may need to be completed very quickly. The latter means that, should attempts at endotracheal intubation fail and the person cannot be ventilated, there is a prospect for neuromuscular recovery and the onset of spontaneous breathing before low blood oxygen levels occurs. It is better than rocuronium in making it easy to intubate.

Suxamethonium is also commonly used as the sole muscle relaxant during electroconvulsive therapy, favoured for its short duration of action.

Suxamethonium is quickly degraded by plasma butyrylcholinesterase and the duration of effect is usually in the range of a few minutes. When plasma levels of butyrylcholinesterase are greatly diminished or an atypical form is present (an otherwise harmless inherited disorder), paralysis may last much longer, as is this the case in liver failure or in neonates.

Side effects

Side effects include malignant hyperthermia, muscle pains, acute rhabdomyolysis with high blood levels of potassium, transient ocular hypertension, constipation and changes in cardiac rhythm, including slow heart rate, and cardiac arrest. In people with neuromuscular disease or burns, an injection of suxamethonium can lead to a large release of potassium from skeletal muscles, potentially resulting in cardiac arrest. Conditions having susceptibility to suxamethonium-induced high blood potassium are burns, closed head injury, acidosis, Guillain–Barré syndrome, cerebral stroke, drowning, severe intra-abdominal sepsis, massive trauma, myopathy, and tetanus.

Suxamethonium does not produce unconsciousness or anesthesia, and its effects may cause considerable psychological distress while simultaneously making it impossible for a patient to communicate. Therefore, administration of the drug to a conscious patient is contraindicated.

Hyperkalemia

The side effect of high blood potassium may occur because the acetylcholine receptor is propped open, allowing continued flow of potassium ions into the extracellular fluid. A typical increase of potassium ion serum concentration on administration of suxamethonium is 0.5 mmol per liter. The increase is transient in otherwise healthy patients. The normal range of potassium is 3.5 to 5 mEq per liter. High blood potassium does not generally result in adverse effects below a concentration of 6.5 to 7 mEq per liter. Therefore, the increase in serum potassium level is usually not catastrophic in otherwise healthy patients.

Severely high blood levels of potassium will cause changes in cardiac electrophysiology, which, if severe, can result in asystole.

Malignant hyperthermia

Malignant hyperthermia from suxamethonium administration can result in a drastic and uncontrolled increase in skeletal muscle oxidative metabolism. This overwhelms the body's capacity to supply oxygen, remove carbon dioxide, and regulate body temperature, eventually leading to circulatory collapse and death if not treated quickly.

Susceptibility to malignant hyperthermia (MH) is often inherited as an autosomal dominant disorder, for which there are at least six genetic loci of interest, the most prominent being the ryanodine receptor gene (RYR1). MH susceptibility is phenotype and genetically related to central core disease (CCD), an autosomal dominant disorder characterized both by MH symptoms and by myopathy. MH is usually unmasked by anesthesia, or when a family member develops the symptoms. There is no simple, straightforward test to diagnose the condition. When MH develops during a procedure, treatment with dantrolene sodium is usually initiated; dantrolene and the avoidance of suxamethonium administration in susceptible people have markedly reduced the mortality from this condition.

Suxamethonium apnea

The normal short duration of Suxamethonium is due to the rapid metabolism of the drug by non-specific plasma cholinesterases. However plasma cholinesterase activity is reduced in some people due to either genetic variation or acquired conditions, this results in a prolonged duration of neuromuscular block. Genetically ninety six percent of the population have a normal (Eu:Eu) genotype and block duration, however some people have abnormal genes (Ea, Es, Ef) which can be found in varying combinations with the Eu gene or other abnormal genes (see Pseudocholinesterase deficiency). All will result in a longer duration of block from 20 minutes up to several hours. Acquired factors that affect plasma cholinesterase activity include pregnancy, liver disease, kidney failure, heart failure, thyrotoxicosis, cancer and a number of other drugs.

If unrecognized by a clinician it could lead to awareness if anesthesia is discontinued whilst still paralyzed or hypoxemia (and potentially fatal consequences) if artificial ventilation is not maintained. Normal treatment is to maintain sedation and ventilate the patient on an intensive care unit until muscle function has returned. Blood testing for cholinesterase function can be performed.

Mivacurium, a non-depolarizing neuromuscular blocking drug, is also metabolized via the same route with a similar clinical effect in patients deficient in plasma cholinesterase activity.

Deliberate induction of conscious apnea using this drug led to its use as a form of aversion therapy in the 1960s and 1970s in some prison and institutional settings. This use was discontinued after negative publicity concerning the terrifying effects on subjects of this treatment and ethical questions about the punitive use of painful aversion.

Effects

There are two phases to the blocking effect of suxamethonium.

Phase 1 block

Phase 1 blocking has the principal paralytic effect. Binding of suxamethonium to the nicotinic acetylcholine receptor results in opening of the receptor's monovalent cation channel; a disorganized depolarization of the motor end-plate occurs and calcium is released from the sarcoplasmic reticulum.

In normal skeletal muscle, acetylcholine dissociates from the receptor following depolarization and is rapidly hydrolyzed by the enzyme acetylcholinesterase. The muscle cell is then ready for the next signal.

Suxamethonium has a longer duration of effect than acetylcholine, and is not hydrolyzed by acetylcholinesterase. By maintaining the membrane potential above threshold, it does not allow the muscle cell to repolarize. When acetylcholine binds to an already depolarized receptor, it cannot cause further depolarization.

Calcium is removed from the muscle cell cytoplasm independent of repolarization (depolarization signaling and muscle contraction are independent processes). As the calcium is taken up by the sarcoplasmic reticulum, the muscle relaxes. This explains muscle flaccidity rather than tetany following fasciculations.

The results are membrane depolarization and transient fasciculations, followed by paralysis.

Phase 2 block

This phase is not abnormal and is a part of its mechanism of action. It is caused by the blood concentration of suxamethonium exceeding the therapeutic window. Desensitization occurs at the nerve terminal, and the myocyte becomes less sensitive to acetylcholine; the membrane repolarizes and cannot be depolarized again.

Chemistry

Suxamethonium is an odorless, white crystalline substance. Aqueous solutions have a pH of about 4. The dihydrate melts at 160 °C, whereas the anhydrous melts at 190 °C. It is highly soluble in water (1 gram in about 1 mL), soluble in ethyl alcohol (1 gram in about 350 mL), slightly soluble in chloroform, and practically insoluble in ether. Suxamethonium is a hygroscopic compound. The compound consists of two acetylcholine molecules that are linked by their acetyl groups. It can also be viewed as a central moiety of succinic acid with two choline moieties, one on each end.

History

Suxamethonium was first discovered in 1906 by Reid Hunt and René de M. Taveau. When studying the drug, animals were given curare and thus they missed the neuromuscular blocking properties of suxamethonium. Instead in 1949 an Italian group led by Daniel Bovet was first to describe succinylcholine induced paralysis. The clinical introduction of suxamethonium was described in 1951 by several groups. Papers published by Stephen Thesleff and Otto von Dardel in Sweden are important but also to be mentioned is work by Bruck, Mayrhofer and Hassfurther in Austria, Scurr and Bourne in UK, and Foldes in America.

Society and culture

Suxamethonium has been described as a "perfect poison" for murder, and has been used by criminals in murders. Suxamethonium chloride is the INN.

References

UpToDate Contents

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• 1. 成人における迅速導入気管挿管のための神経筋遮断剤（NMBA） neuromuscular blocking agents nmba for rapid sequence intubation in adults
• 2. 重症筋無力症患者に対する麻酔 anesthesia for the patient with myasthenia gravis
• 3. 小児における、アデノイド切除同時施行例を含む扁桃摘出に対する麻酔 anesthesia for tonsillectomy with or without adenoidectomy in children
• 4. 成人における選択的脊椎手術のための麻酔 anesthesia for elective spine surgery in adults
• 5. 小児に対する急速挿管法（RSI） rapid sequence intubation rsi in children

English Journal

• Succinylcholine resistance.

• Ammundsen HB1, Sørensen MK2, Gätke MR2.
• British journal of anaesthesia.Br J Anaesth.2015 Jul 16. pii: aev228. [Epub ahead of print]
• PMID 26183168

• Tugging Force: A new objective index for evaluating acute changes in neuromuscular function in mice.

• Okada S1, Orito K2.
• Journal of pharmacological and toxicological methods.J Pharmacol Toxicol Methods.2015 Jul 16. pii: S1056-8719(15)00085-4. doi: 10.1016/j.vascn.2015.07.003. [Epub ahead of print]
• INTRODUCTION: Many agents, including muscle relaxants, influence neuromuscular function. Although in vitro and in situ measurement systems of skeletal muscular contractility have been developed and in use for years, no convenient device and parameter are available to examine the time course of the a
• PMID 26190647

• [Use of neuromuscular blockers in Brazil].

• Locks GF1, Cavalcanti IL2, Duarte NM2, Cunha RM2, Almeida MC2.
• Revista brasileira de anestesiologia.Rev Bras Anestesiol.2015 Jul 6. pii: S0034-7094(15)00063-X. doi: 10.1016/j.bjan.2015.03.001. [Epub ahead of print]
• The objective of this study was to evaluate how Brazilian anesthesiologists are using neuromuscular blockers (NMB), focusing on how they establish the diagnosis of postoperative residual curarization and the incidence of complications associated with the use of NMB. A questionnaire was sent to anest
• PMID 26160168

Japanese Journal

• がん終末期の幻覚妄想状態に電気痙攣療法が有効であった症例

• 新田 リヱ,平 俊浩,西岡 真美,古口 契児
• Palliative Care Research 6(1), 336-339, 2011
• 【目的】緩和ケア病棟において増悪した幻覚妄想状態に電気痙攣療法(electroconvulsive therapy; ECT)が有効であった症例を経験したので報告する. 【症例】30歳代, 女性. 上行結腸がん再発, 肺転移. 緩和ケア病棟入院18日目に, 幻覚妄想を伴う強い緊張病症状を呈した. 消化管閉塞のため, 内服加療は積極的に行えず, ハロペリドールの点滴加療は奏効しなかった. 患者の苦痛 …
• NAID 130000858769

• ロクロニウムの薬理学的特徴

• 加藤 孝澄
• 日本臨床麻酔学会誌 28(5), 822-827, 2008
•  筋弛緩薬の開発の歴史は, 脱分極性筋弛緩薬スキサメトニウム並みの速い作用発現を実現できる副作用の少ない非脱分極性筋弛緩薬の開発の歴史である. 近年, 本邦でも臨床使用が可能になったロクロニウムは, 投与の工夫でスキサメトニウムに迫る速い作用発現が得られるアミノステロイド構造をもつ非脱分極性筋弛緩薬である. 作用持続時間はスキサメトニウムほど短くないが, 同じ非脱分極性筋弛緩薬ベクロニウムと同程度 …
• NAID 130004892567

• 遺伝性低コリンエステラーゼ血症の1症例

• 新谷 裕,松尾 信昭,箱田 滋,平川 昭彦,中谷 壽男,波田 壽一
• 日本救急医学会雑誌 12(8), 420-423, 2001-08-15
• … In these cases, administration of suxamethonium chloride should be avoided. …
• NAID 10007079181

Related Links

• Suxamethonium chloride | インターネット内の検索結果 ...

ウィキペディアの英語版でSuxamethonium chlorideという用語が挙げてありますが、そこでは、以下の意味で使われています。Suxamethonium chloride (INN), also known as suxamethonium or succinylcholine, is a nicotinic acetylcholine ...

• Suxamethonium chloride - wikidoc

Overview Suxamethonium chloride is a skeletal muscle relaxant, neuromuscular blocking drug that is FDA approved for the treatment of induction of neuromuscular blockade, adjunct to general anesthesia, to facilitate endotracheal ...

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★リンクテーブル★

リンク元	「スキサメトニウム」
関連記事	「chloride」

「スキサメトニウム」

　　[★]

英

suxamethonium

同

サクシニルコリン succinylcholine、塩化サクシニルコリン succinylcholine chloride, SCC

化

塩化スキサメトニウム　suxamethonium chloride

商

サクシン、レラキシン、Anectin

関

薬理学

[show details]

スキサメトニウム : 約 4,120 件
サクシニルコリン : 約 1,860 件

分類

• 筋弛緩薬

• 脱分極性筋弛緩薬

作用機序

• アセチルコリン受容体に結合してシナプス後膜を脱分極したままにし、興奮伝達を遮断する。

動態

• 血漿中及び肝臓のpseudocholine esterase(偽ChE)によって分解されるので、持続時間が5分と短い

適応

• 麻酔時の筋弛緩

気管内挿管時・骨折脱臼の整復時・喉頭痙攣の筋弛緩

精神神経科における電撃療法の際の筋弛緩

腹部腫瘤診断時

副作用

SAN.71改変

• 1. 筋肉痛：強い攣縮が起こるために筋痛をきたす。

• a) 外眼筋攣縮：眼圧亢進を来たし、緑内障を生ずることがある。この眼圧亢進は投与後1-6分で5-10mmHgほど上昇
• b) 脳圧亢進
• c) 腹筋の攣縮：胃内圧亢進を来たす。　

• 2. 副交感神経刺激：アセチルコリンと同様の作用を有する　→　ムスカリン作用が強く出現し、徐脈、不整脈を起こしやすい
• 3. 高カルシウム血症
• 4. 悪性過高熱(malignant hyperthermia, 悪性高熱)

治療：ダントロレン：筋小胞体からのカルシウム遊離を阻害

「chloride」

　　[★] 塩素イオン